A Multi-action and Multi-target RuII-PtIV Conjugate Combining Cancer-Activated Chemotherapy and Photodynamic Therapy to Overcome Drug Resistant Cancers

被引：190

作者：

Karges, Johannes ^{[1
]}

Yempala, Thirumal ^{[2
]}

Tharaud, Mickael ^{[3
]}

Gibson, Dan ^{[2
]}

Gasser, Gilles ^{[1
]}

机构：

[1] PSL Univ, Chim ParisTech, Inst Chem Life & Hlth Sci, CNRS,Lab Inorgan Chem Biol, F-75005 Paris, France

[2] Hebrew Univ Jerusalem, Inst Drug Res, Sch Pharm, IL-91120 Jerusalem, Israel

[3] Univ Paris, Inst Phys Globe Paris, CNRS, F-75005 Paris, France

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2020年 / 59卷 / 18期

基金：

欧盟地平线“2020”; 以色列科学基金会; 欧洲研究理事会;

关键词：

bioinorganic chemistry; metals in medicine; photodynamic therapy; platinum prodrugs; POLYPYRIDYL COMPLEXES; ANTICANCER ACTIVITY; PT(IV) DERIVATIVES; METAL-COMPLEXES; IN-VIVO; RUTHENIUM(II); CISPLATIN; AGENTS; APOPTOSIS; PLATINUM;

D O I：

10.1002/anie.201916400

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Pt-II complexes are commonly used to treat cancer. To reduce their side effects and improve their pharmacological properties, Pt-IV complexes are being developed as prodrug candidates that are activated by reduction in cancer cells. Concomitantly, Ru-II polypyridine complexes have gained much attention as photosensitizers for use in photodynamic therapy due to their attractive characteristics. In this article, a novel Pt-IV-Ru-II conjugate, which combines cancer activated chemotherapy with PDT, is presented. Upon entering the cancer cell, the Pt-IV centre is reduced to Pt-II and the axial ligands including the Ru-II complex and phenylbutyrate are released. As each component has its individual targets, the conjugate exerts a multi-target and multi-action effect with (photo-)cytotoxicity values upon irradiation up to 595 nm in the low nanomolar range in various (drug resistant) 2D monolayer cancer cells and 3D multicellular tumour spheroids.

引用

页码：7069 / 7075

页数：7

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